The 14-3-3 protein family includes seven highly conserved dimeric isoforms (β, γ, ε, ζ, η, σ, and τ) that are expressed in all eukaryotic cells (1). Through interaction with phospho-serine or phospho-threonine motifs, 14-3-3 can regulate diverse cellular functions, including signal transduction, cytoskeletal configuration, metabolism, differentiation, survival, and transcription (2). 14-3-3 proteins are implicated in tumorigenesis (3, 4), as a tumor suppressor in the case of 14-3-3σ (SFN), and as a putative oncoprotein in the case of 14-3-3ζ (YWHAZ). 14-3-3σ expression is inhibited in premalignant and malignant cells (5), and loss of 14-3-3σ results in polyploidy and failure to maintain G2/M cell-cycle arrest after DNA damage through cytoplasmic sequestration of CDC2/cyclin B1 (6, 7). 14-3-3ζ expression is up-regulated in various cancers (8), and it induces epithelial-mesenchymal transition by activation of TGF-β/Smads and inhibits apoptosis in anoikic cells, thereby potentiating tumor invasion and metastasis (9, 10).
Endometrial stromal sarcoma (ESS) is a type of uterine sarcoma that, in its low-grade form, contains JAM fusions with various polycomb complex proteins (SUZ12, PHF1, and EPC1) (11, 12). In contrast, some ESS are histologically high grade, and these tumors typically lack JAZF1 rearrangement. The genetic basis for high-grade ESS is undefined.